Lomefloxacin HCl

Uses

Lomefloxacin is used orally in adults for the treatment of mild to moderate lower respiratory tract infections (acute bacterial exacerbations of chronic bronchitis) and uncomplicated or complicated urinary tract infections caused by susceptible organisms. The drug also is used orally for perioperative prophylaxis in patients undergoing transrectal prostate biopsy or transurethral surgical procedures.

Respiratory Tract Infections

Lomefloxacin is used for the treatment of mild to moderate acute exacerbations of chronic bronchitis caused by susceptible Haemophilus influenzae or Moraxella catarrhalis. Because Streptococcus pneumoniae exhibits resistance to lomefloxacin in vitro and the safety and efficacy of the drug in lower respiratory tract infections caused by this organism have not been demonstrated, the drug should not be used for the empiric treatment of respiratory tract infections, including acute bacterial exacerbations of chronic bronchitis, when it is probable that S. pneumoniae is the causative organism.

If empiric therapy is to be undertaken and lomefloxacin therapy is considered, it should be guided by a Gram stain of the sputum; the drug should only be considered for such therapy if the Gram stain demonstrates an adequate quality of specimen (e.g., greater than 25 polymorphonuclear neutrophils per low-power field) and there is a predominance of gram-negative bacteria and not a predominance of gram-positive bacteria.

When lomefloxacin is used for the treatment of UTIs caused by Ps. aeruginosa, the possibility of associated bacteremia should be considered; the manufacturer warns that safety and efficacy of the drug in the treatment of pseudomonal bacteremia have not been established, and serum concentrations achieved with currently recommended oral dosages of lomefloxacin do not reliably exceed the MIC for this organism.

Perioperative Prophylaxis

When lomefloxacin is used perioperatively to reduce the incidence of UTIs in patients undergoing transrectal prostate biopsy, the drug usually is administered as a single dose 1-6 hours prior to the procedure in an attempt to reduce infections that might develop during the early (3-5 days) and late (3-4 weeks) postoperative period.

When lomefloxacin is used perioperatively to reduce the incidence of UTIs in patients undergoing transurethral surgical procedures, the drug usually is administered as a single dose 2-6 hours prior to the procedure in an attempt to reduce infections that might develop during the early postoperative period (3-5 days).

Efficacy of the drug in reducing the incidence of early postoperative infections other than UTIs has not been established. Lomefloxacin should not be used prophylactically in patients undergoing minor urologic procedures, such as simple cystoscopy or retrograde pyelography, for which prophylaxis is not indicated.

Gonorrhea and Associated Infections

Oral lomefloxacin is one of several single-dose alternative regimens recommended by the US Centers for Disease Control and Prevention (CDC) for the treatment of uncomplicated cervical, urethral, or rectal gonorrhea in adults and adolescents.

The CDC states that, although the single-dose lomefloxacin regimen appears to be effective for the treatment of uncomplicated gonorrhea, clinical experience with the regimen is limited and it does not appear to offer any advantage over currently recommended single-dose regimens of ciprofloxacin, ofloxacin, or levofloxacin. In addition, the fact that strains of Neisseria gonorrhoeae with decreased susceptibility to fluoroquinolones have been reported in several areas in the US (e.g., Hawaii, Ohio) and elsewhere (e.g., Southeast Asia, Australia, Africa, Great Britain) should be considered.

The CDC states that fluoroquinolones should not be used for the treatment of gonococcal infections acquired in Asia or the Pacific islands (including Hawaii) and may be inadvisable for infections acquired in other areas where N. gonorrhoeae with fluoroquinolone resistance have been reported (including California).

Cautions

Lomefloxacin generally is well tolerated, and adverse effects of the drug are similar to those reported with other fluoroquinolones; however, lomefloxacin appears to be associated with a higher frequency of photosensitivity reactions. Most adverse effects reported in clinical trials have been mild to moderate in severity and transient. Adverse effects have been reported in 2-12% of patients, and have resulted in discontinuance in 2-4% of patients. The most frequent adverse effects of the drug involve the skin, nervous system, and GI tract.

Dermatologic and Sensitivity Reactions

Lomefloxacin appears to be associated with a higher frequency of photosensitivity reactions than other currently available fluoroquinolones. Current evidence suggests that quinolone-induced photosensitivity may be either phototoxic or photoallergic in nature; however, the manufacturer states that all photosensitivity reactions reported to date with lomefloxacin have been phototoxic.

Photosensitivity reactions were reported in 2.3% of patients in clinical trials with the drug. Moderate to severe photosensitivity reactions (e.g., erythema, edema, blistering, bullous eruptions, rash, pruritus, dermatitis, eczematous lesions) have occurred in patients exposed to direct or indirect sunlight or to artificial (ultraviolet, UV) light (e.g., sunlamps) during or following therapy with lomefloxacin and can occur following a single dose of the drug.

These reactions also have occurred in patients exposed to shaded or diffuse light, including exposure through glass, and with or without the use of sunscreens. Recovery may be prolonged for several weeks in some cases. As with some other types of photosensitivity, exacerbation of the reaction on reexposure to sunlight or artificial (UV) light before complete recovery is possible. Rarely, reactions have recurred up to several weeks after discontinuing the drug.

Exposure to direct or indirect sunlight (even when using sunscreens) should be avoided while receiving lomefloxacin and for several days after treatment, and therapy with the drug should be discontinued immediately at the first sign of photosensitivity. Limited evidence indicates that the minimal dose of UVA light needed to result in erythema (MED-UVA) is inversely proportional to plasma concentrations of lomefloxacin. In healthy individuals receiving lomefloxacin (at steady-state), the MED-UVA values 16 and 12 hours postdose were substantially higher than values obtained 2 hours postdose.

These results indicate that increasing the time interval between administration of lomefloxacin and exposure to UVA light increases the amount of light energy needed for photoreaction. Pruritus (including genital itching), rash (e.g., erythematous), urticaria, eczema, skin exfoliation, diaphoresis, and other skin disorders have been reported in less than 1% of patients treated with lomefloxacin.

Occasionally, such dermatologic reactions may result in discontinuance of the drug. Although not reported in clinical studies with lomefloxacin, erythema nodosum, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, and hyperpigmentation have been reported with other quinolones. Serious and potentially fatal hypersensitivity (anaphylactoid or anaphylactic) reactions, sometimes occurring following the first dose, have been reported in patients receiving quinolones, including lomefloxacin.

Such reactions may be accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, or pruritus and most frequently have been reported in patients without a history of hypersensitivity reactions. If an allergic reaction occurs during lomefloxacin therapy, the drug should be discontinued. Severe acute hypersensitivity reactions should be treated with appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, IV fluids, antihistamines, maintenance of blood pressure) as indicated. Chills, allergic reaction, and facial edema have been reported in less than 1% of patients receiving lomefloxacin.

Nervous System Effects

Headache and dizziness are the most common adverse CNS effects of lomefloxacin, occurring in 3-9% and 2-7% of patients, respectively, in clinical trials, and occasionally they may result in discontinuance of the drug. Adverse nervous system effects that have been reported in less than 1% of patients receiving the drug include coma, hyperkinesia, tremor, twitching, 1 vertigo, paresthesia, somnolence, insomnia, nervousness, confusion, anxiety, asthenia, fatigue, malaise, depression, agitation, depersonalization, paranoid reaction, abnormal thinking, impaired concentration, and paroniria.

Psychiatric disturbances, agitation, anxiety, and sleep disorders may be more common with lomefloxacin than with other quinolones. Although not reported in clinical trials with lomefloxacin, possible exacerbation of myasthenia gravis, hallucinations, manic reaction, ataxia, phobia, and dysphasia have been reported with other quinolones. Seizures have been reported in patients receiving lomefloxacin, but it has not been established whether they were directly related to the drug.

Seizures, increased intracranial pressure, toxic psychoses, and CNS stimulation, which may lead to tremor, restlessness, lightheadedness, confusion, and hallucinations, have been reported in patients receiving other quinolones.

Lomefloxacin has been associated with a possible increased risk of seizures compared with other quinolones; these may occur with a relative absence of predisposing factors. If any of these reactions occurs in patients receiving lomefloxacin, the drug should be discontinued and appropriate treatment initiated. Pending availability of additional information, lomefloxacin should be used with caution in patients with known or suspected CNS disorders.

GI Effects

Nausea, diarrhea, and abdominal pain are the most common adverse GI effects of lomefloxacin, occurring in 3.5-7%, 1-3%, and 1.2% of patients, respectively, in clinical trials, and these effects occasionally may require discontinuance of therapy with the drug. Dyspepsia, vomiting, flatulence, constipation, GI inflammation, dysphagia, GI bleeding, dry mouth, tongue discoloration, dysgeusia, anorexia, stomatitis, and increased appetite have been reported in less than 1% of patients receiving lomefloxacin. Although not reported in clinical trials with lomefloxacin, painful oral mucosa and intestinal perforation have been reported with other quinolones.

Effects on GI Flora

Lomefloxacin exerts a selective effect on normal bowel flora. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including lomefloxacin. However, while fluoroquinolones, including lomefloxacin, are relatively inactive against Clostridium difficile in vitro, pseudomembranous colitis has been reported relatively infrequently with the drugs. Broad-spectrum anti-infectives may alter normal GI flora and lead to overgrowth of Clostridium difficile and production of the toxin thought to result in pseudomembranous colitis.

The possibility that diarrhea developing in any lomefloxacin-treated patient may be secondary to C. difficile-associated pseudomembranous colitis should be considered. Mild cases of colitis may respond to discontinuance of lomefloxacin alone, but diagnosis and management of moderate to severe cases should include appropriate examination and bacteriologic studies as well as treatment with fluid, electrolyte, and protein supplementation as indicated. If colitis is moderate to severe or is not relieved by discontinuance of lomefloxacin, appropriate anti-infective therapy (e.g., metronidazole, vancomycin) should be administered. Isolation of the patient may be advisable.

Other causes of colitis also should be considered. Total bacterial counts of normal anaerobic fecal flora generally are unaffected by lomefloxacin use. Gram-positive aerobic oral flora also are unaffected by the drug or may increase (mainly streptococci).

Cardiovascular Effects

Hypotension, hypertension, edema, syncope, flushing, tachycardia, bradycardia, arrhythmia, extrasystoles, cyanosis, cardiac failure, angina pectoris, myocardial infarction, pulmonary embolism, cerebrovascular disorder, cardiomyopathy, and phlebitis have been reported in less than 1% of patients receiving lomefloxacin. Although not reported in clinical trials with lomefloxacin, cardiopulmonary arrest and cerebral thrombosis have been reported with other quinolones.

Hepatic Effects

Increases in serum concentrations of ALT (SGPT), AST (SGOT), bilirubin, and alkaline phosphatase have been reported in less than 1% of patients receiving lomefloxacin. Increased serum concentrations of Gamma-glutamyltransferase (?-glutamyl transpeptidase, GGT, GGTP) have been reported rarely.Although not reported in clinical trials with lomefloxacin, hepatic necrosis has been reported with other quinolones.

Hematologic Effects

Thrombocytopenia, thrombocythemia, purpura, lymphadenopathy, increased fibrinolysis, anemia, and monocytosis have been reported in less than 1% of patients receiving lomefloxacin. Prolongation of prothrombin time, leukocytosis, leukopenia, eosinophilia, decreased hemoglobin, hemolytic anemia, macrocytosis, and elevated erythrocyte sedimentation rate (ESR) have also been reported. Although not reported in clinical trials with lomefloxacin, agranulocytosis has been reported with other quinolones.

Musculoskeletal Effects

Leg cramps, arthralgia, chest or back pain, nonspecific pain, and myalgia have been reported in less than 1% of patients treated with lomefloxacin. Achilles, shoulder, and hand tendon ruptures that required surgical repair or resulted in prolonged disability have been reported in patients receiving fluoroquinolones, including lomefloxacin. Lomefloxacin should be discontinued in any patient who experiences pain, inflammation, or rupture of a tendon. Tendon rupture can occur during or following therapy with lomefloxacin. Lomefloxacin, like most other fluoroquinolones (e.g., ciprofloxacin, gatifloxacin, moxifloxacin, levofloxacin, norfloxacin, ofloxacin), causes arthropathies in immature animals of various species. (See Cautions: Pediatric Precautions.)

Ocular Effects

Abnormal vision, conjunctivitis, photophobia, abnormal lacrimation, and ocular pain have been reported in less than 1% of patients receiving lomefloxacin. Although not reported in clinical trials with lomefloxacin, diplopia, nystagmus, and photophobia have been reported with some other quinolones. Ophthalmologic abnormalities, including lenticular opacities, were not observed in lomefloxacin-treated animals in studies designed to evaluate such effects or in subchronic and chronic toxicity studies in rats, dogs, and monkeys.

Genitourinary and Renal Effects

Vaginitis, dysmenorrhea, leukorrhea, intermenstrual bleeding, perineal pain, and vaginal candidiasis have been reported in less than 1% of women and orchitis and epididymitis have been reported in less than 1% of men receiving lomefloxacin. Dysuria, hematuria, strangury, micturition disorder, albuminuria, and anuria have also been reported in less than 1% of patients receiving lomefloxacin.

Abnormal urinary specific gravity and increased BUN have been reported rarely. Although not reported in clinical trials with lomefloxacin, candiduria, crystalluria, polyuria, interstitial nephritis, renal failure, renal calculi, and urinary retention have been reported with other quinolones. Crystalluria was not observed in lomefloxacin-treated animals in studies designed to evaluate such an effect or in subchronic and chronic toxicity studies in rats, dogs, and monkeys.

Respiratory Effects

Dyspnea, respiratory infection, rhinitis, pharyngitis, epistaxis, respiratory disorder, respiratory depression, bronchospasm, cough, increased sputum, and stridor have been reported in less than 1% of patients receiving lomefloxacin. Although not reported in clinical trials with lomefloxacin, pulmonary edema has been reported with other quinolones.

Decreased total serum protein or albumin concentration, decreased serum potassium or other abnormalities in serum electrolyte concentrations, and decreased blood glucose concentration have been reported rarely. Although not reported in clinical trials with lomefloxacin, acidosis, laryngeal edema, hiccups, and elevated serum triglyceride concentration, serum cholesterol concentration, serum potassium concentration, and blood glucose concentration have been reported with other quinolones.

Precautions and Contraindications

Lomefloxacin is contraindicated in patients with a history of hypersensitivity to the drug or to other quinolones. Lomefloxacin, like other quinolones, may cause serious, potentially fatal hypersensitivity reactions, occasionally following the initial dose. (See Cautions: Dermatologic and Sensitivity Reactions.) Patients should be advised of this possibility and instructed to discontinue the drug and contact their physician at the first sign of rash or any other sign of hypersensitivity.

Because lomefloxacin may cause moderate to severe photosensitivity reactions, patients should be advised to avoid to the maximum extent possible direct or indirect sunlight (including exposure through glass and exposure through sunscreens) and artificial (UV) light (e.g., sunlamps) during and for several days after therapy with the drug. (See Cautions: Dermatologic and Sensitivity Reactions.)

Patients also should be advised to discontinue lomefloxacin immediately and contact a physician at the first sign of a photosensitivity reaction such as sensation of skin burning, edema, blistering, rash, pruritus, or dermatitis.

Patients who have experienced a photosensitivity reaction should be advised to avoid reexposure to sunlight and artificial (UV) light until the reaction has resolved completely, since reactions have recurred rarely up to several weeks after discontinuing lomefloxacin therapy. Because lomefloxacin, like other quinolones, may cause increased intracranial pressure, toxic psychoses, and CNS stimulation that potentially could result in tremor, restlessness, lightheadedness, mental confusion, hallucinations, and/or seizures, pending availability of additional information the drug should be used with caution in patients with known or suspected CNS disorders, such as severe cerebral arteriosclerosis or seizure disorders, or other factors (e.g., concomitant drug therapy) that predispose to seizures. If any of these CNS reactions occur in patients receiving lomefloxacin, the drug should be discontinued and appropriate treatment initiated.

Patients should be advised that lomefloxacin may cause dizziness or lightheadedness, and their individual susceptibility to these adverse effects should be determined before operating a motor vehicle or machinery or engaging in activities requiring mental alertness and coordination.

Although crystalluria has not been reported in clinical trials with lomefloxacin, patients should be instructed to drink sufficient quantities of fluids to ensure proper hydration and adequate urinary output during therapy with the drug. Patients receiving lomefloxacin should be advised to discontinue the drug and inform their clinician if they experience pain, inflammation, or rupture of a tendon and to rest and refrain from exercise until a diagnosis of tendonitis or tendon rupture is excluded.

Doses and/or frequency of administration of lomefloxacin should be decreased in patients with severe renal impairment since plasma concentrations of the drug are higher and prolonged in such patients compared with patients with normal renal function. Serial determinations of plasma lomefloxacin concentration should be performed to determine whether any adjustment in the usual dosing interval is necessary.

As with other anti-infectives, use of lomefloxacin may result in overgrowth of nonsusceptible organisms. Resistant strains of some organisms may develop during therapy with the drug. If superinfection occurs, appropriate therapy should be instituted. Specialized references and/or the manufacturer’s labeling should be consulted for information on potential drug interactions and laboratory test interferences

Pediatric Precautions

Safety and efficacy of lomefloxacin in children younger than 18 years of age have not been established. Because lomefloxacin, like most other fluoroquinolones, causes arthropathy in immature animals of various species, some clinicians state that the drug should not be used in children younger than 16-18 years of age.

Other clinicians suggest that fluoroquinolones may be used cautiously in adolescents if skeletal growth is complete and suggest that the potential benefits of therapy with these drugs may outweigh the possible risks in certain children 9-18 years of age with serious infections (e.g., cystic fibrosis patients) when the causative organism is resistant to other available anti-infectives.

The American Academy of Pediatrics (AAP) states that use of fluoroquinolones (e.g., ciprofloxacin, levofloxacin, lomefloxacin, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin) in children younger than 18 years of age may be justified in special circumstances; however, the drugs should be used only after careful assessment of the risks and benefits for the individual patient and after these benefits and risks have been explained to the parents or caregivers. The AAP states that fluoroquinolones may be useful when no other oral agent is available (to avoid use of a parenteral agent) or when the pediatric patient has an infection caused by multidrug-resistant gram-negative bacteria, such as certain strains of Pseudomonas, or Mycobacterium.

Therefore, possible uses of fluoroquinolones in pediatric patients include the treatment of urinary tract infections caused by P. aeruginosa or other multidrug-resistant gram-negative bacteria, chronic suppurative otitis media or malignant otitis externa, chronic osteomyelitis, exacerbation of cystic fibrosis, mycobacterial infection, or other gram-negative bacterial infections in immunocompromised patients when prolonged oral therapy is desired. Arthropathy, involving multiple diarthrodial joints, and lameness were observed in immature dogs administered lomefloxacin at oral dosages as low as 4.5 mg/kg for 7-8 days (0.3 times the recommended human adult dosage based on mg/m2 or 0.6 times the recommended human adult dosage based on mg/kg).

Arthropathy and lameness also were observed in rats receiving oral dosages of the drug at 5.4 times the recommended human adult dosage (based on mg/m2; 34 times the recommended human adult dosage based on mg/kg). Histopathologic examination of the weight-bearing joints in these animals revealed permanent erosions of the cartilage. In immature rats, no changes were observed in the joints at dosages up to 91 mg/kg for 7 days (2 times the recommended human dosage based on mg/m2; 11 times the recommended human dosage based on mg/kg).

Geriatric Precautions

Lomefloxacin generally is well tolerated in geriatric patients. When the total number of patients studied in clinical trials of lomefloxacin is considered, 25% were 65 years of age or older and 9% were 75 years of age or older.

Although no overall differences in efficacy or safety were observed between geriatric and younger patients and other clinical experience has not revealed evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.

Lomefloxacin is substantially eliminated by the kidney and the risk of toxic reactions to the drug may be greater in patients with impaired renal function. Because geriatric patients are more likely to have decreased renal function, lomefloxacin dosage should be selected carefully and it may be useful to monitor renal function in these patients. Dosage of lomefloxacin does not need to be modified in geriatric patients with creatinine clearances of at least 40 mL/minute per 1.73 m.

Mutagenicity and Carcinogenicity

The CHO/HGPRT in vitro mutagenicity assay was weakly positive at lomefloxacin concentrations of 226 g/mL and higher and negative at concentrations lower than 226 g/mL. Lomefloxacin was not mutagenic in 2 other in vitro mutagenicity assays (tests for chromosomal aberrations in Chinese hamster ovary cells or human lymphocytes) and in 2 in vivo mouse micronucleus mutagenicity tests. In a study in hairless (Skh-1) mice exposed to UVA light for 3.5 hours 5 times every 2 weeks for up to 52 weeks while concomitantly receiving lomefloxacin or other quinolones, skin tumors developed in a substantial proportion of the treated mice. The lomefloxacin dosages used in this study caused a phototoxic response.

The time to development of skin tumors was 16 weeks in mice treated with UVA light and lomefloxacin concomitantly compared with 28-52 weeks when other quinolones were used concomitantly with such light.

Almost all (92%) of the mice treated concomitantly with UVA light and lomefloxacin developed well-differentiated squamous cell carcinomas of the skin, which were nonmetastatic and endophytic in character; two-thirds of these carcinomas contained large central keratinous masses and were thought to arise from the vestigial hair follicles in the hairless animals. In this model, mice treated with lomefloxacin alone did not develop skin or systemic tumors. There are no data available from similar models using pigmented and/or fully haired mice. The clinical importance of these findings to humans is not known.

Pregnancy, Fertitlity and Lactation

There are no adequate and well-controlled studies to date using lomefloxacin in pregnant women.

Since lomefloxacin, like most other fluoroquinolones, causes arthropathy in immature animals, the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. Reproduction studies in rats using lomefloxacin dosages up to 34 times the recommended human dosage (on a mg/kg basis; 8 times the recommended human dosage based on a mg/m2 basis) have not revealed harm to the fetus.

An increased incidence of fetal loss was observed in monkeys receiving 6-12 times the recommended human lomefloxacin dosage (on a mg/kg basis; approximately 3-8 times the recommended human dosage on a mg/m2 basis), but no teratogenicity was observed in rats and monkeys receiving up to 16 times the recommended human dosage. Studies in rabbits showed maternal toxicity and associated fetotoxicity, decreased placental weight, and variations of the coccygeal vertebrae at 2 times the recommended human lomefloxacin dosage (on a mg/m2 basis).

Reproduction studies in male and female rats using oral lomefloxacin dosages up to 34 times the recommended human dosage (on a mg/kg basis; 8 times the recommended human dosage on a mg/m2 basis) have not revealed evidence of impaired fertility. It is not known whether lomefloxacin is distributed into human milk, although it is known that some fluoroquinolones are distributed into human milk and that lomefloxacin is distributed into milk in lactating rats. Because of the potential for serious adverse reactions to lomefloxacin in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Description

Lomefloxacin is a fluoroquinolone anti-infective agent. Like other commercially available fluoroquinolones, lomefloxacin contains a fluorine at the C-6 position of the quinolone nucleus; however, like sparfloxacin, lomefloxacin contains a second fluorine group.

For additional information on this drug until a more detailed monograph is developed and published, the manufacturer’s labeling should be consulted. It is essential that the labeling be consulted for information on the usual cautions, precautions, and contraindications concerning potential drug interactions and/or laboratory test interferences and for information on acute toxicity.